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, 17 (1), 52-63

Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

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Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

Yi-Chao Shi et al. Genomics Proteomics Bioinformatics.

Abstract

Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.

Keywords: Fecal; Gastric mucosal; Gastroesophageal reflux disease; Microbiota; Proton pump inhibitors.

Figures

Figure 1
Figure 1
Characteristics of gastric mucosal microbial diversity in GERD patients with PPI use A. Four metrics of alpha diversity (Chao1 estimator richness, observed species, Shannon index, and Simpson index) were calculated in gastric mucosal samples. Two-tailed Wilcoxon rank sum tests were performed to assess differences between the non-PPI-user, PPI-user, and HC groups. The middle line in the box plot represents the median value, and the box is drawn from the 25% to 75% quartiles. Whiskers show the minimum and maximum values, and the ends of the whiskers represent the nonoutlier range. B. PCoA of an unweighted UniFrac analysis plot based on the relative taxa abundance in the gastric mucosal microbiota of GERD patients and HCs. Each symbol represents a sample. PPI, proton pump inhibitor; GERD, gastroesophageal reflux disease; HC, healthy control; PCoA, principal component analysis.
Figure 2
Figure 2
Characteristics of fecal microbial diversity in GERD patients with PPI use A. Alpha diversity plots of Chao1 estimator richness, observed species, Shannon index, and Simpson index measures for fecal samples in the non-PPI-user, PPI-user, and HC groups. Wilcoxon rank sum tests were used to determine the significance of the differences between groups. B. PCoA of unweighted UniFrac analyses of the differences in the fecal microbiota between non-PPI-user or PPI-user GERD patients and the HC group. PC1 and PC2 represent the two highest discriminating axes. The corresponding subject’s number is adjacent to each symbol.
Figure 3
Figure 3
Characteristics of the microbial composition in GERD patients with PPI use A. Relative abundance of the dominant bacteria at phylum level in the gastric mucosal microbiota of GERD patients with or without PPI use and the HC group. B. Relative abundance of the dominant bacteria at phylum level in the fecal microbiota of GERD patients with or without PPI use and the HC group. C. Relative abundance of the top 35 dominant bacteria at genus level in the gastric mucosal microbiota of GERD patients with or without PPI use and the HC group.
Figure 4
Figure 4
Variations in the gastric mucosal microbiota in GERD patients with PPI use A. Cladogram derived from LEfSe analysis of metagenomic sequences of gastric mucosal samples from HCs and GERD patients. The prefixes “p”, “c”, “o”, “f”, and “g” indicate the phylum, class, order, family, and genus, respectively. B. LEfSe comparison of the microbiota in gastric samples from GERD patients with or without PPI use and the HC group. Enriched taxa in samples from GERD patients and HCs with different classification levels with an LDA score >3.0 are shown. C. Extended error bar plots showing functional properties that differ between the gastric mucosal microbiota of non-PPI-users, short-term PPI-users, and long-term PPI-users. LEfSe, linear discriminant effect size; LDA, linear discriminant analysis.
Figure 5
Figure 5
Variations in the fecal microbiota in GERD patients with PPI use A. LEfSe comparison of the microbiota in fecal samples from GERD patients with or without PPI use and the HC group. Enriched taxa in samples from GERD patients and HCs with different classification levels with an LDA score >3.0 are shown. B. Cladogram plotted based on LEfSe analysis showing the taxonomic levels represented by rings, with phyla in the outermost ring and genera in the innermost ring. Each circle represents a member within that level. The taxa at each level are colored according to abundance (P < 0.05; LDA score >3). C. Extended error bar plots showing significantly different microbiota between non-PPI-user, short-term PPI-user, and long-term PPI-user with an effect size ≥1%.
Figure 6
Figure 6
PICRUSt analysis predicts functional composition in GERD patients with PPI use A. Predicted functional composition of metagenomes based on 16S rRNA gene sequencing data from the gastric mucosal microbiota. Pathway enrichment for KEGG metabolic pathways followed by statistical comparative analysis using LEfSe were performed to determine differential enrichment between the non-PPI-user, PPI-user, and HC groups. B. Predicted metabolic functions of the fecal bacterial communities were generated with LEfSe based on the PICRUSt dataset, showing significantly differing abundance in GERD patients with or without PPI use and HCs.

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References

    1. Jung H.K. Epidemiology of gastroesophageal reflux disease in Asia: a systematic review. J Neurogastroenterol Motil. 2011;17:14–27. - PMC - PubMed
    1. Jo Y., Park E., Ahn S.B., Jo Y.K., Son B., Kim S.H. A proton pump inhibitor's effect on bone metabolism mediated by osteoclast action in old age: a prospective randomized study. Gut Liver. 2015;9:607–614. - PMC - PubMed
    1. Reimer C. Safety of long-term PPI therapy. Best Pract Res Clin Gastroenterol. 2013;27:443–454. - PubMed
    1. Atkinson N.S., Reynolds D.J., Travis S.P. 'Lemonade Legs': why do some patients get profound hypomagnesaemia on proton-pump inhibitors? Intest Res. 2015;13:227–232. - PMC - PubMed
    1. Xu H.B., Wang H.D., Li C.H., Ye S., Dong M.S., Xia Q.J. Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis. Genet Mol Res. 2015;14:7490–7501. - PubMed

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